Evaluation of Osteoporotisis Drugs by Histological, Biochemical Approach in Experimental Osteoporosis Model

实验性骨质疏松模型中通过组织学、生化方法评价骨质疏松药物

• 批准号: 16591470
• 负责人: ITOI Eiji
• 金额: $ 0.9万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591470/
• 关键词: vitamin D; osteoporosis; muscle strength; muscle fatigue; ビタミンK

Several recent studies have demonstrated that vitamin D affects not only bone but also muscle to prevent falls and osteoporotic fractures. However, these effects on muscle and the mechanisms of fall-prevention are still unclear. In this study, we investigated the effects of alfacalcidol (1α(OH)D3) on muscle strength, muscle fatigue, and bone mineral density (BMD) in normal and ovariectomized rats.Following ovariectomy (OVX) or sham operation in 7-month-old female Wistar rats, alfacalcidol (0.1 μg/kg/day) or its vehicle was administered orally for 4 weeks. On the day after the final administration, the distal end of the Achilles' tendon was cut and attached to a force transducer under general anesthesia, and the sciatic nerve was exposed and electrically stimulated for 20 cycles. The maximum contraction tension of the calf muscles for each stimulation cycle was measured to evaluate muscle strength. Muscle fatigue at each stimulation cycle was evaluated as the percentage strength at each cycle to the initial contraction strength. Muscle strength and fatigue were then normalized using the body weight. After the measurement of muscle strength and fatigue, the right femur was harvested to measure the BMD at the distal third of the femur by dual energy x-ray absorptiometry.Alfacalcidol administration significantly increased the maximum muscle strength in the sham-operated and the OVX groups compared to their respective control groups. However, alfacalcidol administration did not significantly affect muscle fatigue in these groups. The BMD in the alfacalcidol-treated OVX group was significantly higher than that in the vehicle-treated OVX group.We conclude that alfacalcidol increases muscle strength, but does not affect muscle fatigue in the rat model. The effectiveness of vitamin D in preventing fractures may be partly due to its effect on muscle strength in addition to its known effect on bone metabolism.

最近的几项研究表明，维生素 D 不仅影响骨骼，还影响肌肉，以预防跌倒和骨质疏松性骨折。然而，这些对肌肉的影响以及预防跌倒的机制仍不清楚。在这项研究中，我们研究了阿法骨化醇的作用。 1α(OH)D3) 对正常和卵巢切除大鼠的肌肉力量、肌肉疲劳和骨矿物质密度 (BMD) 的影响。7 个月大雌性 Wistar 进行卵巢切除 (OVX) 或假手术后给大鼠口服阿法骨化醇（0.1μg/kg/天）或其载体，持续4周。在最后一次给药后的第二天，在全身麻醉下切开跟腱远端并将其连接到力传感器上。暴露坐骨神经并电刺激20个周期，测量每个刺激周期小腿肌肉的最大收缩张力，以评估每个刺激周期的肌肉疲劳程度，以每个周期的强度百分比来评估。然后使用体重将肌肉力量和疲劳标准化。测量肌肉力量和疲劳后，采集右股骨，通过双能 X 射线骨密度测定法测量股骨远端 1/3 处的 BMD。与各自的对照组相比，阿法骨化醇给药显着增加了假手术组和OVX组的最大肌肉力量，但是，阿法骨化醇给药并没有显着影响这些组的肌肉疲劳。阿法骨化醇治疗的 OVX 组显着高于媒介物治疗的 OVX 组。我们得出的结论是，阿法骨化醇增加了大鼠模型的肌肉力量，但不影响肌肉疲劳。维生素 D 在预防骨折方面的有效性可能是部分的。由于其对肌肉力量的影响以及对骨代谢的已知影响。